Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus.

Abstract

Tryptophan-derived indole compounds have been widely investigated as antioxidants and as free-radical scavengers. Indole-3-propionic acid (IPA), one of these compounds, is a deamination product of tryptophan. In the present study, we used Mongolian gerbils to investigate IPA's neuroprotective effects against ischemic damage and its antioxidative effects in the hippocampal CA1 region (CA1) after 5 min of transient forebrain ischemia. The repeated oral administration of IPA (10 mg/kg) for 15 days before ischemic surgery protected neurons from ischemic damage. In this group, the percentage of cresyl violet-positive neurons in the CA1 was 56.8% compared with that in the sham group. In the vehicle-treated group, glial fibrillary acidic protein (GFAP)-, S-100-, and vimentin-immunoreactive astrocytes and ionized calcium-binding adapter molecule 1 (Iba-1)- and isolectin B4 (IB4)-immunoreactive microglia were activated 4 days after ischemia/reperfusion, whereas in the IPA-treated ischemic group, GFAP, S-100, Iba-1, and IB4, but not vimentin, immunoreactivity was distinctly lower than that in the vehicle-treated ischemic groups. The administration of IPA significantly decreased the level of 4-hydroxy-2-nonenal, a marker of lipid peroxidation, in ischemic hippocampal homogenates compared with that in the vehicle-treated ischemic groups at various times after ischemia/reperfusion. In addition, immunostaining for 8-hydroxy-2'-deoxyguanosine showed DNA damage in pyramidal neurons in the ischemic CA1 was significantly lower in the IPA-treated ischemic groups than in the vehicle-treated ischemic groups. These results suggest that IPA protects neurons from ischemia-induced neuronal damage by reducing DNA damage and lipid peroxidation.

• Authors: In Koo Hwang, Ki-Yeon Yoo, Hua Li, Ok Kyu Park, Choong Hyun Lee, Jung Hoon Choi, Young-Gil Jeong, Yun Lyul Lee, Young-Myeong Kim, Young-Guen Kwon, Moo-Ho Won
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 87 Issue 9 Pg. 2126-37 (Jul 2009) ISSN: 1097-4547 [Electronic] United States
• PMID: 19235887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2009 Wiley-Liss, Inc.

Chemical References

• Biomarkers
• Indoles
• Neuroprotective Agents
• indolepropionic acid

Topics

• Administration, Oral
• Animals
• Astrocytes (drug effects, metabolism, pathology)
• Biomarkers (analysis, metabolism)
• DNA Damage (drug effects)
• Disease Models, Animal
• Gerbillinae
• Gliosis (drug therapy, physiopathology, prevention & control)
• Hippocampus (drug effects, metabolism, physiopathology)
• Hypoxia-Ischemia, Brain (drug therapy, metabolism, physiopathology)
• Indoles (pharmacology)
• Lipid Peroxidation (drug effects, physiology)
• Male
• Microglia (drug effects, metabolism, pathology)
• Nerve Degeneration (drug therapy, metabolism, physiopathology)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects, physiology)
• Treatment Outcome